Over four million men, women and infants suffer from chlamydial genital infection annually. Women bear a special burden because of their increased risk of adverse reproductive consequences. Chlamydia trachomatis is responsible for 25-50% of the estimated one million cases of pelvic inflammatory disease/year. The majority of cases of tubal disease associated with chlamydial salpingitis appear to result from chronic, subclinical infection. Clearly, both humoral and cellular immune mechanisms are important in resolving chlamydial infections, while in other circumstances, contributing to more severe disease. We simply do not understand the immunopathogenesis of C. trachomatis: what chlamydial antigens are exposed on the surface of infected genital cells, how do they get there, and how are they perceived by the host immune system? Can these intracelllular pathogens impose constraints on eukaryotic signals which result in down regulation of Class I and Class II molecules? To complement and add to the information available from endometrial biopsies and animal model studies on T cell responses, our overall goal is to understand the cell and molecular biology of C. trachomatis antigen sorting and secretion. In the first three Specific Aims, we shall use fluorescence and immunoelectron microscopy to determine: (i) what C. trachomatis antigens are secreted to the surface of normally infected versus persistently infected primary human endometrial gland epithelial cells (HEGEC), and if the antigens are directed in a polarized fashion-- to the apical or basolateral surface, or both; (ii) if the chlamydial antigen profile on the surface of infected HEGEC. we shall attempt to identify the T cell subsets activated by secreted chlamydial antigens. In Specific Aim four, the antibodies detecting the chlamydial surface antigens will be used to probe genomic libraries to isolate the genes encoding the proteins for isolation and characterization of the antigenic peptides.